Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MicroRNAs (miRNAs) play pivotal roles in modulating key biological processes in gastric cancer (GC). As a newly identified miRNA, the function and potential mechanism of miR-188-5p in GC has not been thoroughly elucidated. Here, quantitative real-time polymerase chain reaction detection showed abnormally higher expression of miR-188-5p in GC cells and tissues. Gain-of-function analysis in vitro showed that miR-188-5p promoted GC cell proliferation and migration, while loss-of-function studies showed the reverse. Targetscan has predicted that phosphatase and tensin homolog (PTEN) was a potential target gene of miR-188-5p. miR-188-5p suppressed PTEN messenger RNA and protein expression and activated downstream AKT/mTOR signaling in GC cells, but luciferase reporter analysis showed that PTEN was not regulated by miR-188-5p via the 3' untranslated region. Furthermore, we observed that miR-188-5p overexpression promoted Sal-like protein 4 (SALL4) protein expression, cellular nuclear translocation, and transcription. Knockdown of SALL4 eliminated the effect of miR-188-5p in GC cells as well as suppression of PTEN. Taken together, our results demonstrate that miR-188-5p promotes GC cell proliferation and migration while suppressing tumor suppressor gene PTEN expression via transcriptional upregulation of oncogene SALL4. We conclude that miR-188-5p acts as an oncomiRNA in GC and may be a promising therapeutic target for GC.
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PMID:miR-188-5p emerges as an oncomiRNA to promote gastric cancer cell proliferation and migration via upregulation of SALL4. 3100 38

Drug resistance is an important factor for the poor prognosis of non-small cell lung cancer (NSCLC). Sal-like protein 4 (Sall4) is a stem cell marker, and plays a role in maintaining self-renewal. Previous studies have demonstrated that Sall4 may be a candidate for use as support in the diagnosis of lung cancer, and may also represent a therapeutic target. However, the role of Sall4 on drug resistance of lung cancer cells and the mechanism by which Sall4 regulates the sensitivity of lung cancer cells to cisplatin (DDP) remains unknown. In this study, we aim to investigate whether knockdown of Sall4 by siRNA can enhance the apoptosis induced by cisplatin in lung cancer cells. We here reported that the expression of Sall4 was dramatically upregulated in cisplatin-resistant A549 cells compared with the parental cells. Knockdown of Sall4 by siRNA in cisplatin-resistant A549 cells reduced the IC50 compared with the parental cells. In addition, knockdown of Sall4 significantly inhibited cell proliferation, induced apoptosis and invasion cisplatin-resistant A549 cells through AKT/mTOR signaling. Our findings demonstrate that Sall4 is an essential regulator in cisplatin-induced apoptosis, and knockdown of Sall4 may restore cisplatin sensitivity in acquired resistant cells. Thus, our study provides an effective therapeutic strategy for NSCLC treatment.
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PMID:Knockdown of SALL4 overcomes cisplatin-resistance through AKT/mTOR signaling in lung cancer cells. 3193 49